E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary hypercholesterolemia or mixed dyslipidemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058110 |
E.1.2 | Term | Dyslipidemia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of two lipid modifying drugs, fenofibrate (a PPAR-α agonist) and Niaspan (slow release niacin), on HDL-C plasma levels and HDL functionality in patients with low (< 40 mg/dL) and normal (between 40 and 59 mg/dL) HDL-C levels at baseline. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: • To assess the relationship between HDL-C plasma levels and HDL functionality: - Reverse Cholesterol Transport (RCT) as measured by the capacity of serum to promote cell cholesterol efflux from macrophage and hepatoma cells. - HDL particle number, size and composition. • To correlate HDL particule number, size and composition with RCT. • To correlate plasma Apo-AI level with RCT. • To assess the relationship between HDL functionality and the whole lipid profile.
Exploratory objectives: • To explore the effect of fenofibrate and slow release niacin on potential biomarkers of HDL functionality such as the: - Effect on Endothelial Function - Effect on HDL modifying enzymes/transporters - Anti-inflammatory effect - Anti-thrombotic effect - Change in oxidative stress |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and post-menopausal female, lipid treatment naïve or previously treated patients 2. Age 18 - 75 years (inclusive) 3. Low < 40 mg/dL and normal HDL-C levels (between 40 and 59 mg/dL) 4. LDL-C levels: >130 mg/dL, but < 190 mg/dL 5. Triglyceride levels: >150 mg/dL, but <400 mg/dL 6. Written informed consent (approved by the Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures |
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E.4 | Principal exclusion criteria |
1. Subjects with secondary causes for Dyslipidemia (i.e. diabetes mellitus, hypothyroidism, obstructive liver disease, chronic renal failure) 2. Body Mass Index (BMI) ≥ 30 kg/m2 3. Patients requiring drugs that increase LDL-C and decrease HDL-C [progestins, anabolic steroids, and corticosteroids] 4. Patients who drink alcohol excessively, defined as more than 21 units/week for males and more than 14 units/week for females. An alcohol unit is defined as 10 mL of absolute alcohol, 300 mL beer, 25 mL of a single spirit, or 100 mL of wine 5. History of or current alcohol or drug abuse 6. Use of an investigational drug in the 3 months prior to the screening visit 7. Any clinically significant medical condition that could interfere with the conduct of the study 8. Systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg at the screening visit 9. History of obstructive biliary disorders, pancreatitis, collagen diseases, or auto-immune diseases 10. History of malignancy during the 3 years prior to the screening visit 11. Known or suspected diagnosis of hepatitis or human immunodeficiency virus (HIV) infection 12. Known thyroid dysfunction 13. Any past history of cerebro-vascular accident or coronary events, including unstable angina, myocardial infarction, angioplasty, or coronary artery bypass graft 14. Females who are pregnant or breast feeding and females of child bearing potential 15. Clinically significant hepatic, renal or cerebral disease 16. Hepatic transaminases or creatine phosphokinase > 2 times the upper limit of normal (ULN) at the screening visit 17. Unable or unwilling to comply with the protocol requirements, or deemed by the investigator to be unfit for the study 18. Subjects contraindicated for PPAR-α or slow release niacin treatment according to approved label 19. Lipid modifying drugs 20. Any concomitant therapy known to alter any of the parameters to assess (i.e., aspirin, except when aspirin is indicated for the prevention of severe flushes induced by Niaspan) 21. Hypersensitivity to PPARα or slow release niacin |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percent and absolute changes from baseline in HDL-C plasma level will be the primary parameter to assess the direct effect of 6 weeks crossover treatment with two lipid modifying drugs, a PPARα agonist, fenofibrate, and slow release niacin, Niaspan. Due to the exploratory nature of the study no single primary parameter can be identified to assess the effect of 6 weeks crossover treatment with two lipid modifying drugs on HDL-C functionality. The following parameters describing HDL functionality and the reverse cholesterol transport (RCT) will be used as main study endpoints: • HDL particle number, size and composition • ApoA1 protein level • Capacity of serum to promote cell cholesterol efflux from macrophages and hepatoma cells |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |